Project Summary There are currently over 250,000 survivors of childhood cancer in the U.S. Recent diagnostic therapeutic advances in pediatric oncology have led to greater survival rates in children and young adults with malignancies. However, while cancer therapies improve long-term survival, such treatments can lead to impaired fertility potential and eventual premature ovarian failure. The gonadotoxic effects of chemotherapeutic agents are well documented, particularly for alkylating agents such as cyclophosphamide and appear to be dose dependent. However, while reduced reproductive potential has been recognized for many years, little information is known about the endocrinology of hypothalamic-pituitary-gonadal function in adolescents and young adults with cancer prior to, during, and after treatment. In the infertility setting, several clinical tests, including serum hormone measures and ultrasound measures of the ovaries, have been developed and are routinely used as surrogate markers to evaluate a woman's fertility potential and for counseling regarding treatment options. In addition, there is emerging data that markers of oxidative stress may reflect ovarian aging. However, it has not been established that such ovarian function testing can detect diminished fertility potential in young female cancer patients during and after cancer treatment. Early detection of decreased fertility potential in cancer survivors would help to identify individuals who would benefit from aggressive treatment with existing assisted reproductive technologies and emerging novel fertility preserving methods while there is still a chance of a successful pregnancy. The current proposal represents a comprehensive and novel investigation to assess measui fertility potential in adolescent and young adult cancer survivors. The aims are two fold: to compare existing and novel surrogate measures of fertility potential between young female cancer survivors and healthy controls, and to assess changes in existing and novel surrogate measures of fertility potential during and after chemotherapy in young cancer patients. Measures of fertility potential to be tested include ultrasound imaging, endocrine evaluation, and assessment of oxidative stress. This proposal will assist in establishing a protocol for evaluating ovarian reserve in female pedii cancer survivors. Specifically, the results of this proposal will serve as preliminary data for the establishment of a long term cohort study of pediatric cancer survivors to examine the association between these measures and pregnancy rates, pregnancy outcomes and the occurrence of premature menopause.